The proposed research is directed at determining the intracellular events whereby serosal hypertonicicty (SH) elicits in the isolated urinary bladder of amphibia hydrosmotic effects that are similar to those obtained in antidiuretic hormone (ADH). Both stimuli seem to share common final pathways in triggering an increase in water permeability of the apical membrane, but SH may enter the chain of intracellular events at a site distal to the generation of cAMP. Both stimuli have similar cationic requirements with regard to Na ion, K ion, H ion and Ca 2 ion. Prostaglandins (PGE) also may be involved in modulating the effects of SH. An in-depth investigation of the physiological effects of SH and its modulation by different factors will be undertaken and compared to the effects of ADH, exogenous cyclic AMP and/or theophylline in the isolated toad bladder. Specifically: 1) the interactions between the hydrosmotic effects of SH, ADH, exogenous cAMP and theophylline will be defined; 2) the cationic participation of Na ion, K ion, H ion and Ca 2 ion and the role of permeability changes of the basolateral membrane to these cations on the hydrosmotic responses to SH and to ADH and on the interactions between the two hydrosmotic challenges will be determined; 3) the roles of cyclic nucleotides (cAMP and cGMP) and exogenous and endogenous PGE in the permeability changes induced by hypertonicity will be evaluated. 4) In addition, studies of transepithelial sodium transport during SH and ADH challenges in different ionic environments previously tested with regard to water transport will also be performed in an attempt to ascribe the specificity of the effects observed to either information not only on the specificity of the responses. 5) Finally, physiological and morphological correlates of the hydrosmotic response to SH and its modification by different treatments will be investigated by transmission electron microscopy. These studies should provide information not only on the specificity of the responses of the urinary bladder to SH but on the use of SH as a tool in the study of the post-cAMP modulating steps of hormonally induced processes; finally, they could define a model to help evaluate the role of renal inner medulla hypertonicity in the hormonal regulation of the urinary concentration.